title: Paenimacrolidin, a novel macrolide antibiotic from Paenibacillus sp. F6-B70 active against methicillin-resistant Staphylococcus aureus.
abstract: Paenibacillus sp. F6-B70 was selected from several dozens of isolates with activity against methicillin-resistant Staphylococcus aureus using a 16S rDNA-based screening method. F6-B70 contained polyketide synthase (PKS) and non-ribosomal peptide synthetase (NRPS) clusters in its genome revealed by PCR amplification of conserved adenylation and ketosynthase (KS) domains. Phylogenetic data suggested that the strain hosts trans-AT PKSs and their product may be a branched molecule. An antibiotic was subsequently isolated from the methanol extract of F6-B70 cells. The molecular formula of the antibiotic was deduced to be C(33) H(50) NaO(6) ([M + Na](+) , m/z 565.3505) by analysis of electrospray ionization mass spectral data. Elucidation of the structure by nuclear magnetic resonance and infrared spectroscopy revealed that the active compound, paenimacrolidin (PAM), was a novel 22-membered macrolide with side-chains. The new antibiotic, mainly as a bacteriostatic agent, inhibits a couple of multidrug-resistant Staphylococcus sp. strains. The antibiotic capacity of PAM was compromised by its instability, which can be overcome significantly with addition of an anti-oxidant. To our knowledge, this is the first report of the isolation of an active macrolide from paenibacilli, which may be a promising source of novel antibiotics.
authors.affiliation: Institute of Microbiology, College of Life Sciences, Zhejiang University, Hangzhou, China. mblab@163.com
authors.forename: Xue-Chang
authors.initials: XC
authors.lastname: Wu
authors.forename: Chao-Dong
authors.initials: CD
authors.lastname: Qian
authors.forename: Hai-Huan
authors.initials: HH
authors.lastname: Fang
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Wen
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Zhou
authors.forename: Zha-Jun
authors.initials: ZJ
authors.lastname: Zhan
authors.forename: Rui
authors.initials: R
authors.lastname: Ding
authors.forename: Ou
authors.initials: O
authors.lastname: Li
authors.forename: Haichun
authors.initials: H
authors.lastname: Gao
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D016000:Cluster Analysis; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004275:DNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D018942:Macrolides / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D053858:Metabolic Networks and Pathways / Q000235:genetics; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D005810:Multigene Family; D056507:Paenibacillus / Q000145:classification / Q000302:isolation & purification* / Q000378:metabolism*; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D017422:Sequence Analysis, DNA; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared
chemical_list: D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D004275:DNA, Ribosomal; D018942:Macrolides; D012336:RNA, Ribosomal, 16S